Mucus secretion is a normal function of respiratory mucous membranes. Models for measurement of mucus production by cultured human bronchial and nasal mucose have been developed in order to examine the controls of mucus secretion. In addition to neurohormones and mediators of allergy, airways react to products generated by pulmonary macrophages and peripheral mononuclear cells with increased mucous glycoprotein secretion. The macrophage and mononuclear derived secretagogues are collectively being called macrophage/mononuclear cell derived mucus secretagogues (MMS). Both are generated by mononuclear cells phagocytosing zymosan or by surface activation with protein A-containing S. aurius. The generation of MMS is maximal after 4 hours, requires new protein synthesis by a cycloheximide-sensitive pathway and MMS is not stored intracellularly. MMS from mononuclear cells is small (2,000 daltons) and focuses with a PI of 5.1. Activation of complement leads to anaphylatoxin generation. Current studies indicate that anaphylatoxins may be formed in pulmonary inflammatory processes. Therefore, the effects of human C3a upon mucus release were examined. C3a (and C5a) cause a dose-related stimulation of mucus secretion, maximal at 1-4 hours, apparently not requiring mast cell activation and not reproduced by C3a des arg. Thus, complement derived anaphylatoxins may also participate in mucus secretion.